Effects of chronic opioid exposure on guinea pig mu opioid receptor in Chinese hamster ovary cells: comparison with human and rat receptor.
Effects of chronic opioid exposure on guinea pig mu opioid receptor in Chinese hamster ovary cells: comparison with human and rat receptor.
复制标题
慢性阿片类药物暴露对中国仓鼠卵巢细胞中豚鼠 mu 阿片类受体的影响：与人和大鼠受体的比较。
DOI：
10.1016/j.bcp.2007.02.001
复制
发表时间：
2007
影响因子：
5.8
通讯作者：
Olsen,GeorgeD
中科院分区：
文献类型：
--
作者：
Wallisch,Michael;Nelson,ColeS;Mulvaney,JuliaM;Hernandez,HeatherS;Smith,SueAnn;Olsen,GeorgeD
慢性阿片类药物治疗导致μ阿片受体的激动剂特异性作用。慢性阿片类药物暴露的分子机制包括脱敏、内化和下调膜结合μ阿片受体（MOP）。本研究的目的是比较暴露于两种临床上重要的阿片类药物（吗啡和美沙酮）后，豚鼠、人和大鼠MOP在中国仓鼠卵巢（CHO）细胞中表达的细胞调节。MOP表达CHO细胞在培养物中用美沙酮或吗啡处理长达48小时。使用配对对照和阿片样物质暴露的CHO细胞进行放射性配体二丙诺啡和[d-AIa 2，N-Me-Phe 4，Gly 5-ol]-脑啡肽（DAMGO）刺激的GTPγS结合试验。美沙酮诱导的μ阿片受体下调，而吗啡诱导脱敏的受体为所有三个物种。此外，吗啡主要降低DAMGO刺激GTPγS结合的效力，而美沙酮主要降低其效力。DAMGO效力和功效的变化在物种之间存在差异，并取决于用于治疗细胞的阿片类药物。我们的研究结果表明，豚鼠和人MOP之间的相似性吗啡诱导的脱敏，但确定两者之间的差异美沙酮诱导的脱敏。与此相反，人和大鼠MOP不同的吗啡治疗的反应，但在他们的美沙酮治疗的反应并不明显。豚鼠是研究阿片类药物作用的一种良好的动物模型，但迄今为止尚未对其分子阿片药理学进行研究。这些结果可以帮助了解阿片配体激活μ阿片受体的作用的物种差异。
Chronic opioid treatment leads to agonist-specific effects at the mu opioid receptor. The molecular mechanisms resulting from chronic opioid exposure include desensitization, internalization and down-regulation of membrane-bound mu opioid receptors (MOP). The purpose of this study was to compare the cellular regulation of guinea pig, human and rat MOP expressed in Chinese hamster ovary (CHO) cells, following exposure to two clinically important opioids, morphine and methadone. MOP expressing CHO cells were treated in culture with methadone or morphine for up to 48h. Radioligand diprenorphine and [d-AIa2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO)-stimulated GTPγS binding assays were carried out using paired control and opioid-exposed CHO cells. Methadone induced downregulation of the mu opioid receptor, while morphine induced desensitization of the receptor for all three species. Furthermore, morphine predominantly decreased the potency of DAMGO to stimulate GTPγS binding, whereas methadone primarily reduced its efficacy. Changes in DAMGO potency and efficacy differed among species and depended on the opioid used to treat the cells. Our results showed similarities between guinea pig and human MOP for morphine-induced desensitization, but identified differences between the two for methadone-induced desensitization. In contrast, human and rat MOP differed in response to morphine treatment, but were not distinct in their response to methadone treatment. The guinea pig is an excellent and established animal model to study opioid effects, but its molecular opioid pharmacology has not been investigated thus far. These results can assist in understanding species differences in the effects of opioid ligands activating the mu opioid receptor.